Pain is a fundamental experience with a complex and multi-layered neurobiological basis. In recent years a powerful battery of techniques has been brought to bear to unravel the mechanisms by which painful stimuli are transduced and processed. There have been several recent discoveries regarding the molecular transduction mechanisms in nociceptors and novel molecular and cellular mechanisms underlying the spinal processing of painful stimuli. The mechanisms by which sensory neurons initiate hyperalgesia and touch evoked pain (allodynia) have been addressed particularly successfully in recent studies. The rich variety of key molecular players that have emerged in physiological and pathophysiological pain states reflects the sophistication and uniqueness of this vitally important sense.